This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Two mutually exclusive hypotheses have emerged in humans implicating a role of the endogenous opioid (EO) system in (SIB). The pain hypothesis proposes that elevated EOs result in hypoalgesia leading to SIB as a form of self stimulation. In contrast, the self-administration hypothesis proposes that individuals engage in SIB to elevate EOs and relieve negative emotions. Importantly, we have shown that the EO system may be altered in monkeys with SIB. SIB monkeys preferentially directed biting to acupressure points (Marinus et al. 2000), which is thought to involve release of EOs in humans (Ulett et al. 1998). We have also reported reduced levels of plasma beta-endorphin (Tiefenbacher et al. 2003a) and CSF met-enkephalin (Tiefenbacher et al. 2003b) in monkeys with SIB. These findings suggest that SIB in our monkeys may be best explained by the self-administration hypothesis which serves to increase beta-endorphin levels. Based on findings in enkephalin and dynorphin knockout mice, that brain opioid receptors are up-regulated (Brady et al. 1999;Clarke et al. 2003), we hypothesized that mu-opioid receptors (MOR) are up-regulated in the brains of monkeys with SIB, increasing the positive effects of beta-endorphin release after biting.